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Published on: July 21, 2018
Tumor protein D52 (TPD52) affects cancer cell metabolism by negatively regulating AMPK
Yali Chen1, Changmin Peng2, Wei Tan1,2
1Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
Background:
The AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, with deregulation leading to cancer and other diseases. However, how this pathway is dysregulated in cancer has not been well clarified.
Methods:
Using a tandem affinity purification/mass-spec technique and biochemical analyses, we identified tumor protein D52 (TPD52) as an AMPKα-interacting molecule. To explore the biological effects of TPD52 in cancers, we conducted biochemical and metabolic assays in vitro and in vivo with cancer cells and TPD52 transgenic mice. Finally, we assessed the clinical significance of TPD52 expression in breast cancer patients using bioinformatics techniques.
Results:
TPD52, initially identified to be overexpressed in many human cancers, was found to form a stable complex with AMPK in cancer cells. TPD52 directly interacts with AMPKα and inhibits AMPKα kinase activity in vitro and in vivo. In TPD52 transgenic mice, overexpression of TPD52 leads to AMPK inhibition and multiple metabolic defects. Clinically, high TPD52 expression predicts poor survival of breast cancer patients.
Conclusion:
The findings revealed that TPD52 is a novel regulator of energy stress-induced AMPK activation and cell metabolism. These results shed new light on AMPK regulation and understanding of the etiology of cancers with TPD52 overexpression.
Insights
Tumor protein D52 (TPD52) interacts with AMP-activated protein kinase (AMPK) and inhibits its activity. High TPD52 expression in breast cancer correlates with poor survival, revealing TPD52 as a novel regulator of cancer metabolism.
Area of Science:
- Molecular Biology
- Cancer Research
- Metabolic Regulation
Background:
- AMP-activated protein kinase (AMPK) regulates energy homeostasis; its deregulation is linked to cancer.
- Mechanisms of AMPK pathway dysregulation in cancer remain unclear.
Purpose of the Study:
- Identify novel AMPK-interacting molecules in cancer.
- Investigate the biological role of tumor protein D52 (TPD52) in cancer metabolism and progression.
Main Methods:
- Tandem affinity purification/mass spectrometry to identify interacting proteins.
- Biochemical and metabolic assays in vitro and in vivo.
- Analysis of TPD52 transgenic mice.
- Bioinformatic analysis of TPD52 expression in breast cancer patients.
Main Results:
- TPD52 forms a stable complex with AMPK in cancer cells.
- TPD52 directly inhibits AMPKα kinase activity.
- TPD52 overexpression in mice causes AMPK inhibition and metabolic defects.
- High TPD52 expression in breast cancer patients predicts poor survival.
Conclusions:
- TPD52 is a novel regulator of energy stress-induced AMPK activation and cellular metabolism.
- Findings provide insights into AMPK regulation and the role of TPD52 in cancer etiology.
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